First, abbreviations used herein will be described.
CS: Chondroitin sulfate
CS-A: Chondroitin sulfate A (chondroitin 4-sulfate; chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising a glucuronic acid residue and an N-acetylgalactosamine residue sulfated at the C-4 position)
CS-B: Chondroitin sulfate B (dermatan sulfate; chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising an iduronic acid residue and an N-acetylgalactosamine residue sulfated at the C-4 position)
CS-C: Chondroitin sulfate C (chondroitin 6-sulfate; chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising a glucuronic acid residue and an N-acetylgalactosamine residue sulfated at the C-6 position)
CS-D: Chondroitin sulfate D (chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising a glucuronic acid residue sulfated at the C-2 position and an N-acetylgalactosamine residue sulfated at the C-6 position)
CS-E: Chondroitin sulfate E (chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising a glucuronic acid residue and an N-acetylgalactosamine residue sulfated at the C-4 and C-6 positions)
CS-K: Chondroitin sulfate K (chondroitin sulfate containing, as a main constitutional disaccharide unit, a disaccharide structure comprising a glucuronic acid residue sulfated at the C-3 position and an N-acetylgalactosamine residue sulfated at the C-4 position)
EDCI.HCl: 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride
HA: Hyaluronic acid
Crosslinked CS: CS which is crosslinked
Photo crosslinked CS: CS which is crosslinked by irradiation with light
Photocrosslinking reaction: Reaction wherein crosslinking is formed by irradiation with light
Photoreactive group: Residue of a part at which crosslinking is formed in a compound wherein the crosslinking is formed by irradiation with light
Photoreactive CS: CS into which a photoreactive group is introduced and which possesses a property capable of forming crosslinking by irradiation with light
HOSu: N-Hydroxysuccinimide
PBS: Phosphate-buffered physiological saline
PEG: Polyethylene glycol
Moreover, the “nucleus pulposus filler” means a pharmaceutical agent to be packed into an area where nucleus pulposus of an intervertebral disc is present. In this connection, the term “fill” in the present specification and claims is used as a concept including not only the case that a predetermined area is completely charged but also the case that the area is not completely charged.
Deformation of an intervertebral disc is one of major causes of spinal diseases, wherein an area where nucleus pulposus is present and which shows a gel-like property in a normal state loses its gel-like property and thereby symptoms such as pain (e.g., backache) may be induced. Against such pain derived from the deformation of an intervertebral disc, one should perform rehabilitation exercise for controlling the pain or wait the time when the spine is fixed.
If the area where normal nucleus pulposus is to be present can regain a gel-like composition and the composition can be maintained for a long period of time in the deformed intervertebral disc, improvement of pain (backache or the like) over a long period of time can be expected from the biomechanical viewpoint and from the viewpoint of functional maintenance of the intervertebral disc.
Moreover, even in the spinal surgical field, there has been studied tissue regeneration using intervertebral disc cells. If the area where normal nucleus pulposus is to be present can regain a gel-like composition and the composition can be maintained for a long period of time in the deformed intervertebral disc, a good environment for regeneration of nucleus pulposus can be formed over a long period of time and it can be also expected that a good nucleus pulposus is efficiently regenerated.
Furthermore, if the area where nucleus pulposus of an intervertebral disc is to be present can maintain a gel-like composition for a long period of time, there is also a possibility that the deformation of the intervertebral disc can be prevented and spinal diseases themselves can be controlled.
Patent Document 1 discloses restoration of injury and deformation of an intervertebral disc by injecting CS or HA into nucleus pulposus.
However, there is neither disclosure nor suggestion on injection of a crosslinked CS into nucleus pulposus of an intervertebral disc.    Patent Document 1: WO 02/40070 pamphlet